Clazosentan in Reducing Vasospasm-related Morbidity and All-cause Mortality in Adult Patients With Aneurysmal Subarachnoid Hemorrhage Treated by Surgical Clipping (CONSCIOUS-2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Actelion
ClinicalTrials.gov Identifier:
NCT00558311
First received: November 13, 2007
Last updated: March 9, 2012
Last verified: March 2012

November 13, 2007
March 9, 2012
November 2007
July 2010   (final data collection date for primary outcome measure)
Cerebral vasospasm-related morbidity and mortality of all-causes as defined by the protocol [ Time Frame: Within 6 weeks post-aSAH ] [ Designated as safety issue: No ]
Cerebral vasospasm-related morbidity and mortality of all-causes as defined by the protocol [ Time Frame: Within 6 weeks post-aSAH ]
Complete list of historical versions of study NCT00558311 on ClinicalTrials.gov Archive Site
Glasgow Outcome Scale Extended (GOSE) at Week 12 post-aSAH, dichotomized into good (score > 4) and poor (score ≤ 4) outcome. [ Time Frame: Week 12 post-aSAH ] [ Designated as safety issue: No ]
Glasgow Outcome Scale Extended (GOSE) at Week 12 post-aSAH, dichotomized into good (score > 4) and poor (score ≤ 4) outcome. [ Time Frame: Week 12 post-aSAH ]
Not Provided
Not Provided
 
Clazosentan in Reducing Vasospasm-related Morbidity and All-cause Mortality in Adult Patients With Aneurysmal Subarachnoid Hemorrhage Treated by Surgical Clipping
A Prospective, Multi-center, Double-blind, Randomized, Placebo-controlled, Parallel-group Study to Assess the Efficacy and Safety of Clazosentan in Reducing Vasospasm-related Morbidity and All-cause Mortality in Adult Patients With Aneurysmal Subarachnoid Hemorrhage Treated by Surgical Clipping.

The aim of this study is to demonstrate that clazosentan, administered as a continuous intravenous infusion at 5 mg/h until Day 14 post aneurysmal subarachnoid hemorrhage (aSAH), reduces the incidence of cerebral vasospasm -related morbidity and all-cause mortality within 6 weeks post-aSAH treated by surgical clipping. The primary endpoint of the study is the occurrence of cerebral vasospasm-related morbidity, and mortality of all-causes within 6 weeks post-aSAH, defined by at least one of the following:

  1. Death (all causes).
  2. New cerebral infarct(s) due to cerebral vasospasm as either the primary or relevant contributing cause, or not adjudicated to be entirely due to causes other than vasospasm.
  3. Delayed ischemic neurological deficit (DIND) due to cerebral vasospasm as either the primary or relevant contributing cause, or not adjudicated to be entirely due to causes other than vasospasm.
  4. Neurological signs or symptoms (depending on state of consciousness), in the presence of confirmed cerebral vasospasm on angiography (DSA or CTA), leading to the administration of a valid rescue therapy.

An independent Critical Events Committee (CEC) will adjudicate whether or not patients meet the primary endpoint and its individual morbidity components.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Aneurysmal Subarachnoid Hemorrhage
  • Drug: clazosentan
    Intravenous clazosentan administered by continuous infusion at 5 mg/h for the duration of the treatment
  • Drug: placebo
    Placebo administered by continuous infusion at 5 mg/h for the duration of the treatment.
  • Experimental: 1 A
    clazosentan
    Intervention: Drug: clazosentan
  • Placebo Comparator: 2 B
    placebo
    Intervention: Drug: placebo
Macdonald RL, Higashida RT, Keller E, Mayer SA, Molyneux A, Raabe A, Vajkoczy P, Wanke I, Bach D, Frey A, Marr A, Roux S, Kassell N. Clazosentan, an endothelin receptor antagonist, in patients with aneurysmal subarachnoid haemorrhage undergoing surgical clipping: a randomised, double-blind, placebo-controlled phase 3 trial (CONSCIOUS-2). Lancet Neurol. 2011 Jul;10(7):618-25. doi: 10.1016/S1474-4422(11)70108-9. Epub 2011 Jun 2.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1157
July 2010
July 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Males and females aged 18 to 75 years (inclusive).
  2. Patients with a ruptured saccular aneurysm, confirmed by angiography (digital subtraction angiography [DSA] or computed tomography angiography [CTA]), and which has been successfully secured by surgical clipping. The time of aneurysm rupture must be known or possible to estimate with a reasonable degree of certainty.
  3. World Federation of Neurological Surgeons (WFNS) grade I-IV measured prior to the clipping procedure, and which does not worsen to grade V post-procedure (based on regular Glasgow Coma Scale [GCS])*
  4. Patients with any diffuse clot (long axis > or = 20 mm, or any clot present across both hemispheres) on baseline CT scan.
  5. Women of childbearing potential must have a negative serum pregnancy test and must use a reliable method of contraception during the 12 weeks following study drug discontinuation.
  6. Written informed consent to participate in the study must be obtained from the patient or a legal representative prior to initiation of any study-mandated procedure and randomization.

    • Patients must be evaluable for WFNS grade prior to the clipping procedure. Patients who cannot be assessed for WFNS post-procedure due to a requirement for uninterrupted sedation (e.g., for high or unstable intracranial pressure [ICP]) may be included in the study provided that a CT scan is performed at 12 hours post-procedure, but prior to randomization, ruling out any large procedure-related infarct.

Exclusion Criteria:

  1. Patients with subarachnoid hemorrhage (SAH) due to causes other than a saccular aneurysm (e.g., trauma or rupture of fusiform or mycotic aneurysms).
  2. Patients with intraventricular or intracerebral blood, in the absence of subarachnoid blood, or with only a local clot.
  3. Presence of cerebral vasospasm seen on angiography prior to the clipping procedure.
  4. Patients who experienced a major complication during the clipping procedure, such as massive bleeding, major arterial occlusion, a large territorial cerebral infarct defined as involving > 1/3 of a vascular territory, or a new major neurological deficit post-procedure (e.g., hemiplegia or aphasia lasting > or = 12 hours post-aneurysm clipping).*
  5. Patients for whom study drug cannot be started within 56 hours after the aneurysm rupture.
  6. Patients who have had their aneurysm secured by coiling only.
  7. Patients for whom it is known, at the time of screening, that certain follow-up, protocol-mandated imaging assessments will not be feasible.
  8. Patients with hypotension (systolic blood pressure (SBP)< or = 90 mmHg) that is refractory to treatment.
  9. Patients with aspiration pneumonia.
  10. Patients with pulmonary edema or severe cardiac failure requiring inotropic support.
  11. Any severe or unstable concomitant condition or disease (e.g., known significant neurological deficit, cancer, hematological, or coronary disease), or chronic condition (e.g., psychiatric disorder), which, in the opinion of the investigator, would affect the assessment of the safety or efficacy of the study drug.
  12. Significant kidney and/or liver disease, as defined by plasma creatinine > or = 2.5 mg/dL (221 micromol/l) and/or total bilirubin > 3 mg/dL (51.3 micromol/l) measured at the local site laboratory.
  13. Patients receiving i.v. nimodipine, i.v. nicardipine, or fasudil hydrochloride, must have these drugs discontinued at least 4 hours prior to initiation of the study treatment.
  14. Patients receiving statins for less than 2 weeks prior to admission must have them discontinued prior to study drug initiation.
  15. Patients receiving cyclosporin A or other calcineurin inhibitors (e.g., tacrolimus), or patients for whom it is known at the time of randomization that these medications will be started during the study drug infusion period.
  16. Patients who have received an investigational product within 28 days prior to randomization or those who have already participated in the current study.
  17. Patients unlikely to comply with the protocol (e.g., unable to return for follow-up visits).
  18. Known hypersensitivity to other endothelin receptor antagonists.
  19. Patients with current alcohol or drug abuse or dependence.

    • Further detail on exclusion criterion number 4:

      • "Large territorial infarct" refers to those infarcts detected during the clipping procedure or immediately post-procedure (i.e., CT performed for suspicion of cerebral infarct or other complication). This does not imply having to wait 24-48 hours post-procedure to perform the protocol-mandated CT scan in order to randomize a patient.
      • Evaluation for a new major neurological deficit post-procedure implies the reversal of sedation (or waiting for the patient to recover from sedation) and the performance of a GCS examination (verbal scores in intubated patients may be extrapolated from the eye-opening and motor scores using the values provided in the table included in Section 3.9.1.2.1 of the protocol). In the event of a new major neurological deficit that does not improve within 12 hours after the clipping procedure, the patient cannot be included in the study.
Both
18 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Austria,   Belgium,   Canada,   China,   Croatia,   Czech Republic,   Denmark,   Finland,   France,   Germany,   Hong Kong,   India,   Italy,   Korea, Republic of,   Latvia,   New Zealand,   Norway,   Poland,   Russian Federation,   Serbia,   Singapore,   Slovenia,   Spain,   Sweden,   Switzerland,   Turkey,   Ukraine
 
NCT00558311
AC-054-301
Yes
Actelion
Actelion
Not Provided
Study Director: Sebastien Roux, MD Actelion
Actelion
March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP